Review
Medicine, Research & Experimental
Yueran Li, Huifang Xu, Huifang Wang, Kui Yang, Jiajie Luan, Sheng Wang
Summary: Alzheimer's disease is a common neurodegenerative disease that leads to cognitive decline and memory loss. Current treatments only provide symptom relief and do not reverse the disease. Studies have shown that TREM2, predominantly expressed in microglia of the central nervous system, plays a protective role by regulating microglial function and promoting the clearance of toxic substances. However, the specific mechanism of action is not fully understood.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Biochemistry & Molecular Biology
Edward O. Olufunmilayo, R. M. Damian Holsinger
Summary: Alzheimer's disease is the most common form of dementia, with individuals in low- and middle-income countries being the most affected. Variants of the TREM2 receptor have been found to increase the risk of Alzheimer's disease. However, the specific signaling processes triggered by these receptor variants are not well understood.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kathleen M. Schoch, Lubov A. Ezerskiy, Michaela M. Morhaus, Riley N. Bannon, Andrew D. Sauerbeck, Mark Shabsovich, Paymaan Jafar-nejad, Frank Rigo, Timothy M. Miller
Summary: The study found that transient reduction of Trem2 messenger RNA levels in APP/PS1 mice significantly reduced plaque deposition and attenuated microglial association around plaques. The results suggest that Trem2 reduction may activate microglia and aid in plaque removal.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Javier Rueda-Carrasco, Dimitra Sokolova, Sang-Eun Lee, Thomas Childs, Natalia Jurcakova, Gerard Crowley, Sebastiaan De Schepper, Judy Z. Ge, Joanne Lachica, Christina E. Toomey, Oliver J. Freeman, John Hardy, Samuel J. Barnes, Tammaryn Lashley, Beth Stevens, Sunghoe Chang, Soyon Hong
Summary: Neuronal hyperactivity is a key feature in early stages of Alzheimer's disease. Microglia play a potential role in disease risk, and this study found that microglia engulf apoptotic-like spines in response to Aβ oligomer stimulation, thereby reducing synaptic hyperactivity. The findings suggest a beneficial role for microglia in the earliest stages of AD.
Article
Cell Biology
Qi Qin, Zhaoqian Teng, Changmei Liu, Qian Li, Yunsi Yin, Yi Tang
Summary: TREM2 plays a crucial role in the pathogenesis of Alzheimer's disease (AD), influencing microglial functions in amyloid and tau pathologies, inflammatory responses, and metabolism. It may act alone or with other molecules such as apolipoprotein E (APOE) as a multifaceted player in microglial functions.
MECHANISMS OF AGEING AND DEVELOPMENT
(2021)
Article
Cell Biology
Audrey Lee-Gosselin, Nur Jury-Garfe, Yanwen You, Luke Dabin, Disha Soni, Sayan Dutta, Jean-Christophe Rochet, Jungsu Kim, Adrian L. Oblak, Cristian A. Lasagna-Reeves
Summary: The study investigated the effects of TREM2 deficiency on tau spreading using a mouse model and found that Trem2(-/-) mice showed attenuated tau pathology in multiple brain regions along with decreased microglial density. The reduced TREM2 signaling impaired microglia activation and their contribution to tau spreading. However, caution should be exercised before targeting TREM2 as a therapeutic entry point for Alzheimer's disease until its involvement in tau aggregation and propagation is better understood.
Article
Multidisciplinary Sciences
Daniel C. Ellwanger, Shoutang Wang, Simone Brioschi, Zhifei Shao, Lydia Green, Ryan Case, Daniel Yoo, Dawn Weishuhn, Palaniswami Rathanaswami, Jodi Bradley, Sara Rao, Diana Cha, Peng Luan, Shilpa Sambashivan, Susan Gilfillan, Samuel A. Hasson, Ian N. Foltz, Menno van Lookeren Campagne, Marco Colonna
Summary: TREM2 plays a critical role in microglia activation trajectories, with ligand engagement being essential for certain activation pathways. Activation trajectories induced by stimuli are more prominent in female mice than male mice. Injection of hT2AB can replenish depleted microglial pools lacking certain activation trajectories.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Clinical Neurology
Rebecca L. Winfree, Mabel Seto, Logan Dumitrescu, Vilas Menon, Philip De Jager, Yanling Wang, Julie Schneider, David A. Bennett, Angela L. Jefferson, Timothy J. Hohman
Summary: This study investigated the correlation between region-specific TREM2 mRNA expression and neuropathology measures in a large sample size. The results showed that TREM2 expression was related to Alzheimer's disease pathology, cerebrovascular pathology, microglial activation, and cognitive decline, but the associations varied across different brain regions. These findings suggest that TREM2's pathological associations are dependent on the brain region.
ACTA NEUROPATHOLOGICA
(2023)
Article
Neurosciences
Bing Zhu, Yan Liu, Spring Hwang, Kailey Archuleta, Huijie Huang, Alex Campos, Rabi Murad, Juan Pina-Crespo, Huaxi Xu, Timothy Y. Huang
Summary: This study found that Trem2 deletion can enhance the spreading of tau in the brain of mice, leading to impaired synaptic function and memory. Furthermore, Trem2 deletion can strengthen the ability of microglia to transmit tau through exosomal vesicles.
MOLECULAR NEURODEGENERATION
(2022)
Article
Neurosciences
Chao-Ji Yu, Meng Wang, Rui-Yang Li, Tao Wei, Han-Chen Yang, Yun-Si Yin, Ying-Xin Mi, Qi Qin, Yi Tang
Summary: This review summarizes the main characteristics of synapses and synaptic plasticity under physiological and pathological conditions. It elaborates on the role of microglia and the signaling pathways involved in regulating synaptic plasticity. The review also highlights the unique role of TREM2 in microglia-mediated regulation of synaptic plasticity and its relationship with AD, as well as proposing four possible ways in which TREM2 is involved in regulating synaptic plasticity.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Geriatrics & Gerontology
Guy C. Brown, Peter St George-Hyslop
Summary: TREM2 is a pattern recognition receptor expressed on myeloid cells that plays a crucial role in Alzheimer's disease. Soluble TREM2 (sTREM2) has a protective effect by blocking Aβ fibrillization and neurotoxicity. Higher levels of sTREM2 are associated with slower progression of AD.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Neurosciences
Alma S. Popescu, Claire A. Butler, David H. Allendorf, Thomas M. Piers, Anna Mallach, Julian Roewe, Peter Reinhardt, Alessandro Cinti, Loredana Redaelli, Christophe Boudesco, Laurent Pradier, Jennifer M. Pocock, Peter Thornton, Guy C. Brown
Summary: R47H TREM2 may increase the risk of AD by enhancing the phagocytosis of synapses and neurons through greater activation by phosphatidylserine. WT TREM2 may decrease the microglial phagocytosis of synapses and neurons via cystatin F.
Article
Clinical Neurology
Daniel L. Kober, Melissa D. Stuchell-Brereton, Colin E. Kluender, Hunter B. Dean, Michael R. Strickland, Deborah F. Steinberg, Samantha S. Nelson, Berevan Baban, David M. Holtzman, Carl Frieden, Jennifer Alexander-Brett, Erik D. Roberson, Yuhua Song, Tom J. Brett
Summary: The study using comprehensive biolayer interferometry analysis revealed that TREM2 binds apoE through a protein-mediated mechanism, with slight affinity differences among isoforms; TREM2 and sTREM2 can directly bind mAβ42 and potently inhibit Aβ42 polymerization, suggesting a potential role in preventing AD pathogenesis.
ALZHEIMERS & DEMENTIA
(2021)
Review
Neurosciences
Jinchao Hou, Yun Chen, Gary Grajales-Reyes, Marco Colonna
Summary: This review summarizes the mechanisms of microglial response in AD pathology, with a focus on the impact of microglial triggering receptor expressed on myeloid cells 2 (TREM2) on AD pathology in mice and humans. The implications of these recent discoveries on potential therapeutic strategies for AD are also discussed.
MOLECULAR NEURODEGENERATION
(2022)
Article
Neurosciences
Peng Zhao, Yuanzhong Xu, Lu-Lin Jiang, Xuejun Fan, Zhiqiang Ku, Leike Li, Xiaoye Liu, Mi Deng, Hisashi Arase, Jay-Jiguang Zhu, Timothy Y. Huang, Yingjun Zhao, Chengcheng Zhang, Huaxi Xu, Qingchun Tong, Ningyan Zhang, Zhiqiang An
Summary: This study elucidated the molecular mechanisms of LILRB2-mediated inhibition of TREM2 signaling in microglia and demonstrated a novel approach to enhance microglial functions by blocking LILRB2-ligand interactions. The LILRB2 antagonist antibody rescued the inhibition of TREM2 signaling by LILRB2, suggesting a potential therapeutic strategy for improving microglial functions.
MOLECULAR NEURODEGENERATION
(2022)
Article
Chemistry, Multidisciplinary
Jingyi Liu, Chao Liu, Jinfeng Zhang, Yunming Zhang, Keyin Liu, Ju-Xian Song, Sravan Gopalkrishnashetty Sreenivasmurthy, Ziying Wang, Yesi Shi, Chengchao Chu, Yang Zhang, Caisheng Wu, Xianhua Deng, Xingyang Liu, Jing Song, Rongqiang Zhuang, Shugiong Huang, Pengfei Zhang, Min Li, Lei Wen, Yun Wu Zhang, Gang Liu
Article
Biochemistry & Molecular Biology
Zhouyi Rong, Baoying Cheng, Li Zhong, Xiaowen Ye, Xin Li, Lin Jia, Yanfang Li, Francis Shue, Na Wang, Yiyun Cheng, Xiaohua Huang, Chia-Chen Liu, John D. Fryer, Xin Wang, Yun-wu Zhang, Honghua Zheng
Article
Biochemistry & Molecular Biology
Dongdong Zhao, Yunqiang Zhou, Yuanhui Huo, Jian Meng, Xiaoxia Xiao, Linkun Han, Xian Zhang, Hong Luo, Dan Can, Hao Sun, Timothy Y. Huang, Xin Wang, Jie Zhang, Fa-rong Liu, Huaxi Xu, Yun-wu Zhang
Summary: In this study, RPS23RG1 was found to play a role in tauopathies by regulating the degradation of p35 and suppressing Cdk5 activation to inhibit tau hyperphosphorylation. Reduced levels of RPS23RG1 trigger aberrant Cdk5-p35 activation, leading to tau hyperphosphorylation and impaired axon outgrowth. These findings suggest that RPS23RG1 may serve as a potential therapeutic target in tauopathy disorders.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Cell Biology
Zhaoji Liu, Jinhuan Ning, Xiaoyuan Zheng, Jian Meng, Linkun Han, Honghua Zheng, Li Zhong, Xiao-Fen Chen, Xian Zhang, Hong Luo, Dan Can, Huaxi Xu, Yun-wu Zhang
CELL DEATH & DISEASE
(2020)
Article
Cell Biology
Mengxi Niu, Naizhen Zheng, Zijie Wang, Yue Gao, Xianghua Luo, Zhicai Chen, Xing Fu, Yanyan Wang, Ting Wang, Manqing Liu, Tingting Yao, Peijie Yao, Jian Meng, Yunqiang Zhou, Yunlong Ge, Zhanxiang Wang, Qilin Ma, Huaxi Xu, Yun-wu Zhang
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Cell Biology
Yuanhui Huo, Yue Gao, Qiuyang Zheng, Dongdong Zhao, Tiantian Guo, Shuo Zhang, Yuzhe Zeng, Yiyun Cheng, Huaping Gu, Lishan Zhang, Bin Zhu, Hong Luo, Xian Zhang, Ying Zhou, Yun-wu Zhang, Hao Sun, Huaxi Xu, Xin Wang
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Chemistry, Multidisciplinary
Yang Shen, Linbin Li, Xiaoxia Xiao, Sihan Yang, Yuhui Hua, Yinglu Wang, Yun-wu Zhang, Yandong Zhang
Summary: The study demonstrates a unique photochemical desaturation strategy for efficient synthesis of Illicium sesquiterpenes, including a 13-step gram-scale synthesis of (-)-merrilactone A using inexpensive starting materials.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Hongfeng Zhang, Yujuan Hong, Weijie Yang, Ruimin Wang, Ting Yao, Jian Wang, Ke Liu, Huilong Yuan, Chaoqun Xu, Yuanyuan Zhou, Guanxian Li, Lishan Zhang, Hong Luo, Xian Zhang, Dan Du, Hao Sun, Qiuyang Zheng, Yun-Wu Zhang, Yingjun Zhao, Ying Zhou, Huaxi Xu, Xin Wang
Summary: Loss-of-function mutations in SNX14 lead to severe cerebellar ataxia by disrupting axonal transport and mitochondrial function, ultimately affecting Purkinje cells and causing the pathogenesis of the disease.
NATIONAL SCIENCE REVIEW
(2021)
Article
Cell Biology
Yue Wei, Menghui Ma, Sheng Lin, Xin Li, Yue Shu, Ziwei Wang, Yuhang Zhou, Banglian Hu, Baoying Cheng, Shengshun Duan, Xiaohua Huang, Huaxi Xu, Yun-Wu Zhang, Honghua Zheng
Summary: Recent research has found that shedding of CSF1R and TREM2 may play a role in neurodegenerative diseases, particularly the CSF1R I794T variant. Inhibition of shedding was shown to decrease cleaved fragments associated with the I794T variant, suggesting that the cleaved ectodomain fragment may serve as a diagnostic biomarker for ALSP.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Immunology
Baoying Cheng, Xin Li, Kai Dai, Shengshun Duan, Zhouyi Rong, Yingmin Chen, Liangcheng Lu, Zhaoji Liu, Xiaohua Huang, Huaxi Xu, Yun-Wu Zhang, Honghua Zheng
Summary: TREM2 and CSF1R interact directly in microglia cells, modulating their expression levels. Administration of CSF1 partially restores the survival ability of Trem2-deficient microglia, showing potential therapeutic intervention in TREM2 variant-bearing patients with a high risk of Alzheimer's disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Muxian Zhang, Yunqiang Zhou, Yiru Jiang, Zhancheng Lu, Xiaoxia Xiao, Jinhuan Ning, Hao Sun, Xian Zhang, Hong Luo, Dan Can, Jinsheng Lu, Huaxi Xu, Yun-wu Zhang
Summary: The study compared sexual dimorphism in gene expression across primary neurons, astrocytes, and microglia derived from neonatal mouse brains, revealing different levels of sexually dimorphic genes in these primary cells, with enrichment in immune-related pathways. The sexually dimorphic genes were predominantly located on the Y chromosome, and overexpression of Eif2s3y specifically affected synaptic transmission in male neurons and caused autism-like behaviors in male mice, providing new insights into sex differences in neurological disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Xuan Sheng, Yunling Yao, Ruizhi Huang, Ying Xu, Yifei Zhu, Linting Chen, Lianshuai Zhang, Wanbing Wang, Rengong Zhuo, Dan Can, Che-Feng Chang, Yun-Wu Zhang, Huaxi Xu, Guojun Bu, Li Zhong, Xiao-Fen Chen
Summary: The study showed that sTREM2 fragments 41-81 and 51-81 enhanced cell viability and inflammatory responses in primary microglia; fragment 41-81 was more efficient than 51-81 in ameliorating amyloid-related pathology and is a promising candidate for AD therapy.
JOURNAL OF NEUROINFLAMMATION
(2021)
Review
Geriatrics & Gerontology
Banglian Hu, Shengshun Duan, Ziwei Wang, Xin Li, Yuhang Zhou, Xian Zhang, Yun-Wu Zhang, Huaxi Xu, Honghua Zheng
Summary: CSF1R is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the CNS. Its dysfunction is implicated in neurodegenerative disorders including ALSP and AD. Understanding the pathophysiology of CSF1R is crucial for developing targeted therapies for related neurological diseases.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Clinical Neurology
Ping Lu, Fengpeng Wang, Shuixiu Zhou, Xiaohua Huang, Hao Sun, Yun-Wu Zhang, Yi Yao, Honghua Zheng
Summary: A novel pathogenic missense mutation in the CNTNAP2 gene was found in an infant with spontaneous recurrent seizures and intellectual disability. This mutation led to changes in neuron morphology and function, causing an imbalance in excitatory and inhibitory post-synaptic currents in the neural network, potentially contributing to the occurrence of SRSs.
FRONTIERS IN NEUROLOGY
(2021)
Article
Cell Biology
Jian Meng, Linkun Han, Naizhen Zheng, Hui Xu, Zhaoji Liu, Xian Zhang, Hong Luo, Dan Can, Hao Sun, Huaxi Xu, Yun-wu Zhang
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
